Dysregulation of Nitrosylation Dynamics Promotes Nitrosative Stress and Contributes to Cardiometabolic Heart Failure with Preserved Ejection Fraction.

Background: Recent reports suggest increased myocardial iNOS expression leads to excessive protein -nitrosylation, contributing to the pathophysiology of HFpEF. However, the relationship between NO bioavailability, dynamic regulation of protein -nitrosylation by trans- and de-nitrosylases, and HFpEF pathophysiology has not been elucidated. Here, we provide novel insights into the delicate interplay between NO bioavailability and protein -nitrosylation in HFpEF.

Rapid onset fibrotic remodeling and ventricular dysfunction induced by phenylephrine involve targeted reprogramming of myocyte and fibroblast transcriptomes.

Catecholamine dysregulation is a common feature of multiple acute and chronic cardiac conditions, including heart failure. To investigate the role of altered α-adrenergic stimulation on cardiac function, we developed a short-term exposure model, administering phenylephrine subcutaneously to mice for one week. Compared to vehicle-injected controls, phenylephrine-treated animals exhibited increased ejection fraction, decreased chamber size, diastolic dysfunction and ventricular hypertrophy in the absence of hypertension.

Histone H1.0 couples cellular mechanical behaviors to chromatin structure.

Tuning of genome structure and function is accomplished by chromatin-binding proteins, which determine the transcriptome and phenotype of the cell. Here we investigate how communication between extracellular stress and chromatin structure may regulate cellular mechanical behaviors. We demonstrate that histone H1.

Single-cell transcriptomes in the heart: when every epigenome counts.

The response of an organ to stimuli emerges from the actions of individual cells. Recent cardiac single-cell RNA-sequencing studies of development, injury, and reprogramming have uncovered heterogeneous populations even among previously well-defined cell types, raising questions about what level of experimental resolution corresponds to disease-relevant, tissue-level phenotypes. In this review, we explore the biological meaning behind this cellular heterogeneity by undertaking an exhaustive analysis of single-cell transcriptomics in the heart (including a comprehensive, annotated compendium of studies published to date) and evaluating new models for the cardiac function that have emerged from these studies (including discussion and schematics that depict new hypotheses in the field).

Defining the Boundaries of Polycomb Domains in .

Polycomb group (PcG) proteins are an important group of transcriptional repressors that act by modifying chromatin. PcG target genes are covered by the repressive chromatin mark H3K27me3. Polycomb repressive complex 2 (PRC2) is a multiprotein complex that is responsible for generating H3K27me3.

Structure and function of an ectopic Polycomb chromatin domain.

Polycomb group proteins (PcGs) drive target gene repression and form large chromatin domains. In , DNA elements known as Polycomb group response elements (PREs) recruit PcGs to the DNA. We have shown that, within the (-) Polycomb domain, strong, constitutive PREs are dispensable for Polycomb domain structure and function.